Frontiers in antibiotic alternatives for Clostridioides difficile infection

Table 3 Key experiments in bacteriophage for Clostridioides difficile infection treatment

Phage	Experiment	Finding	Ref.
phiCD140	A single dose of phage treatment for C. difficile infection in hamsters	Surviving of phage treated hamster	[135]
phiCD27	Phage treatment of CDI in an in vitro batch fermentation and human colon model	(1) Reduction of both vegetative cell and toxin A and toxin B productions from C. difficile; and (2) No impact on others gut microbes	[135]
phiCDHM1 to phiCDHM6, and phiCDHS1	(1) Investigation for an effective phage combination; and (2) Phage delivered orally in hamster model every 8 h after C. difficile challenge	(1) Discovery of phage-resistant colonies after a single phage treatment; and (2) Reduction of C. difficile amount and colonization using phage combination in vivo	[124]
phiCDHM1, 2, 5, and 6	(1) Phage treatment before and after the biofilm formation; (2) First time using Galleria mellonella (wax moth) model for C. difficile phage; and (3) Using phage in combination with antibiotics (vancomycin)	(1) Reduction and prevention of the biofilm establishment in vitro; and (2) Disease prevention in the prophylaxis group and increasing the wax moth survival rates	[130]
phiCDHM1, 2, 5, and 6	(1) Optimized temperate phage cocktail to treat in batch fermentation model; and (2) First metagenomic analysis of phage treatment on gut microbiome	(1) C. difficile elimination after 24 h in prophylactic condition while maintain other microbiota components; and (2) No significant impact on other bacterial groups in human gut	[127]
phiCDHS1	Measurement of planktonic and adhered C. difficile cells and free phage to human colon tumorigenic cell line HT-29	(1) Reduction of planktonic and adhered C. difficile; and (2) No cytotoxicity to human cells	[129]
phiCD24-2	(1) Using engineered phage delivered Type 1-B CRISPR system as antimicrobial agent in vitro and in vivo; and (2) Mutation of phage lysogenic gene by the cI repressor and integrase gene deletion	(1) C. difficile eradication effectively in engineered phage comparing with wild-type phage; and (2) Detection of lysogen due to potentially functional complements from C. difficile prophage	[125]

C. difficile: Clostridioides difficile.